Project Summary Continuous-flow (CF) rotary pumps have been widely used to treat patients with end-stage heart failure. However, all existing or developing CF devices have the following clinical limitations: reduced arterial pulsatility, threat of pump thrombosis or hemolysis, risk of syncope and death from backflow during pump stoppage, inability to non-invasively evaluate weanability by pump-off test, narrow operating specifications meaning there is no universal device for use as both left and right ventricular assist devices (LVAD and RVAD, respectively), and potential inlet obstruction from suctioning of left ventricular wall into the inlet. To eliminate or minimize these drawbacks, we are developing an innovative, advanced ventricular assist devices (AVAD), derived from features of Cleveland Clinic's LVAD, RVAD, and continuous-flow total artificial heart (CFTAH). The following goals are attainable: maintain physiological pulsatility, reduce the risk of pump thrombosis or hemolysis, prevent backflow by enabling automatic shutoff, enable non-invasive evaluation of pump weanability, demonstrate wide operating specifications, enabling use of the AVAD as either an LVAD or RVAD, and avoid suction events by automatically attenuating pump output. The goals of this proposal are to address the feasibility of the proposed concept, take the first steps toward refinement, and demonstrate the intended mechanical function in vivo. The Specific Aims are: (1) analyze and refine the pump design features by a computational fluid dynamics study and in vitro testing in a mock circulatory loop, to simulate varying hemodynamic events, (2) fabricate one pump with three-dimensional (3D) printed plastic housing and impellers suitable for preliminary bench studies and one titanium version pump for acute in vivo experiments, (3) perform in vitro system characterization and hemolysis testing to verify AVAD system performance, and (4) evaluate system performance in three acute in vivo experiments under varying physiological perturbations to demonstrate mechanical functional goals and biocompatibility screening. After proving the feasibility of this totally new VAD design in this R21 program, we will apply for an R01 grant to further refine the device design, perform bench endurance testing, and carry out chronic animal studies for biocompatibility testing. The proposed AVAD, with many advanced features, will improve the outcomes of patients with severe heart failure, providing safe and effective cardiac support as a bridge to transplant and/or destination therapy.